| Object:To Set up the experimental animal model of the filial rats exposed clozapine in the pregnant day;to examine the effect of clozapine on filial rats:the physical growth and nerve reflextion in neonatal stage ,as well as the cognitive behavior change in grown-up. By this way we hope to evaluate the effect of the clozapine-exposed in the gestation on the offspring and supply suggestion to pregnant patients in mental disorder .MethodWISTAR female rats, ten weeks age, were divided into three groups :control group, 10mg/kg clozapine-exposed group and 40mg/kg clozapine-exposed group .According to the characteristics of the vaginal smear in the sex period, to cohabit the rats in the ovulatory time and regard this day as the pregnant day 1,the pregnant rats were introperitoneally injected by saline for control group , The treatment groups were administered to 10mg/kg and 40mg/kg cozapine injection according to the weight of the pregnant rats at 8 o'clock from the gestation day 6 to day 15; (there is no pup rats produced from 40mg/kg clozapine-exposed group,so the indexs of offsprings as fellow were estimated from both the control group and 10mg/kg clozapine-exposed group.) the experimental indexs were viewed as fellow:1. physical growth: the weight of filial rats PND4.7.11.17, penna detatchment,insicor eruption, eye opening such on;2. nerve reflection in neonatal age: cliff avoidance,slope turning, Surface righting such on3. cognitive behavior of the grown-up offspringthat the clozapine-exposed in pregnance lead to the the retardation of the weight of filial rats in earlier age.2.nerve reflextion:clozapine-exposed filial rats were not affected on the surface turning,however, the time of cliff avoidance of rats was siginificantly retarded in PND3/9 (F=4.969/4.348,P05) ,and the ratio of positive response of airy turning was decreased in PND7/9 ( X = 7 959/6.457,P<0.05) compared with the control group.3.Behavior of grown-up in filial rats:(l)Activity quantity in different surroundings: the quantity of activity of filial rats in clozapine-exposed group is significantly higher than the control group in different suroungings such as inchambA(F=56.558,p<0.01);chambB(F=8.75,P<0.05).(2)spatial learning and memory:In the cued condition, the avoidance latency in the colzapine-exposed group was significantly shorter than the control group in the block 2(p<0.05),however there is no difference on block 3 between two groups;In the place condition,the clozapine-exposed group prrferred to finding the submerged platform in the serial blocks(P<0.01);in reversal condition,the filial rats exposed the clozapine had no advantage on finding out the submerged platform in block2,3,4 except of the block l(p<0.01),the further statistic analysis reminded that it is just the first trial that the filial rats in clozapine-exposed group had the advantage to find out the submerged platform in reversal condition (F=4.86, PO.01) .it isimplicated that the clozapine exposed in the gestation lead to the improvement on the acquiry and consolidation.however the acquired memory seems not to be maintained.Conclusion:Clozapine applying in gestation lead to the impairment of the development and the change of cognitive behavior of the filial rats.
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